Liothyronine

Identification

Summary

Liothyronine is a thyroid hormone replacement therapy used to treat hypothyroidism, to suppress TSH, and to help in the diagnosis of hyperthyroidism.

Brand Names
Cytomel, Np Thyroid
Generic Name
Liothyronine
DrugBank Accession Number
DB00279
Background

Liothyronine is a thyroidal hormone T3 which is normally produced by the thyroid gland in a ratio 4:1 when compared with T4: T3. Liothyronine is the active form of thyroxine which is composed in a basic chemical structure by a tyrosine with bound iodine.3 The exogenous liothyronine product was developed by King Pharmaceuticals and FDA approved in 1956.8

Type
Small Molecule
Groups
Approved, Vet approved
Structure
Weight
Average: 650.9735
Monoisotopic: 650.790038137
Chemical Formula
C15H12I3NO4
Synonyms
  • 3,3',5-triiodo-L-thyronine
  • 3,5,3'-Triiodo-L-thyronine
  • 3,5,3'-Triiodothyronine
  • 4-(4-hydroxy-3-iodophenoxy)-3,5-diiodo-L-phenylalanine
  • L-3,5,3'-Triiodothyronine
  • L-T3
  • Liothyronine
  • Liothyroninum
  • Liotironina
  • O-(4-hydroxy-3-iodophenyl)-3,5-diiodo-L-tyrosine
  • T3
  • Triiodothyronine
External IDs
  • NSC-80203

Pharmacology

Indication

Liothyronine is officially approved for the following indications:

  • Replacement therapy in primary (thyroidal), secondary (pituitary) and tertiary (hypothalamic) congenital or acquired hypothyroidism.

  • As an adjunct therapy to surgery and radioiodine in the management of thyroid cancer.

  • As a diagnostic agent in suppression tests for mild hyperthyroidism or thyroid gland autonomy.Label

In general terms, exogenous liothyronine is used to replace insufficient hormonal production and restore T3 plasma levels.3

The lack of liothyronine can be presented as a pale and puffy face, coarse, brittle hair, dry skin, croaky voice and constipation as well as irregular periods, drowsiness, and lethargy.3

Liothyronine should never be used in the suppression of benign nodules and nontoxic diffuse goiter in iodine-sufficient patients nor in the treatment of hyperthyroidism during the recovery phase of subacute thyroiditis.Label

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatEuthyroid goiterCombination Product in combination with: Levothyroxine (DB00451)••••••••••••
Diagnostic agentHyperthyroidism••••••••••••
Used in combination to manageHypothyroidismCombination Product in combination with: Levothyroxine (DB00451)••••••••••••
Management ofHypothyroidism••••••••••••
Treatment ofMyxedema coma•••••••••••••••••••••• •••••••••• ••••••••
Associated Therapies
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

In hormonal replacement, liothyronine is more potent and present a faster action when compared to levothyroxine but the time of action is significantly shorter. The type of treatment needs to be well evaluated as the fast correction of thyroid hormones in certain diseases presents additional risks such as heart failure.3 The onset of activity is observed a few hours after administration and the maximum effect is observed after 2-3 days.Label

Treatment with liothyronine has been shown to produce normal plasma levels of T3 hormone but to have no effect on the T4 plasma concentration.5

Mechanism of action

Liothyronine replaces endogenous thyroid hormone and then exerts its physiologic effects by controlling DNA transcription and protein synthesis. This effect on DNA is obtained by the binding of liothyronine to the thyroid receptors attached to DNA. Exogenous liothyronine exerts all the normal effects of the endogenous thyroid T3 hormone. Hence, it increases energy expenditure, accelerates the rate of cellular oxidation stimulating growth, maturation, and metabolism of the body tissues, aids in myelination of nerves and development of synaptic processes in the nervous system and enhances carbohydrate and protein metabolism.2

TargetActionsOrganism
AThyroid hormone receptor alpha
agonist
Humans
AThyroid hormone receptor beta
agonist
Humans
UProliferating cell nuclear antigen
antagonist
Humans
Absorption

Thyroid hormones are well absorbed orally. From these hormones, liothyronine is almost completely absorbed and it does not present changes in the absorption rate due to concomitant administration of food.6liothyronin Multiple administration of 50 mcg of liothyronine provided a maximal plasma concentration of total T3 of 346 ng/dL in about 2.5 hours with an AUC of 4740 ng.h/dL.1

Volume of distribution

The reported volume of distribution of liothyronine is reported to be of 0.1-0.2 L/kg.7

Protein binding

Liothyronine presents a very large binding to plasma proteins and around 99.7% of the administered dose can be found bound.4 Liothyronine is found to be bound to thyroxine-binding globulin, thyroxine-binding prealbumin and albumin. It is important to consider that only the little unbound portion of liothyronine is metabolically active.9

Metabolism

Liothyronine is mainly metabolized in the liver where it is deiodinated to diiodothyronine and monoiodothyronine followed by conjugation with glucuronides and sulfates.9 One of the formed metabolites formed by the conjugation and decarboxylation is tiratricol. The iodine released by the metabolism of liothyronine is later taken and used within the thyroid cells.7

Hover over products below to view reaction partners

Route of elimination

The main elimination of thyroid hormones is known to be done via the kidneys from which less than 2.5% of the excreted drug is represented by the unchanged drug. This elimination route is reduced with age. A portion of the metabolic products of liothyronine is excreted to the bile and gut where they can be part of enterohepatic recirculation.9

Half-life

The half-life of liothyronine is reported to be between 1 and 2 days.4

Clearance

There are no reports obtaining this value specifically.

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

The reported oral LD50 of liothyronine in the rat is higher than 4540 mg/kg. When overdosage is registered, symptoms of hyperthyroidism are reported as well as confusion, disorientation, cerebral embolism, seizure, shock, coma, and death. The symptoms of overdose can be presented immediately or several days after overdose ingestion. In an overdose state, reduce the dose of liothyronine and do supportive treatment.Label

There are no reports studying the carcinogenic, and mutagenic potential nor on the effects of liothyronine on fertility.Label

Pathways
PathwayCategory
Thyroid Hormone SynthesisMetabolic
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirLiothyronine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcalabrutinibThe therapeutic efficacy of Liothyronine can be decreased when used in combination with Acalabrutinib.
AcamprosateThe excretion of Acamprosate can be decreased when combined with Liothyronine.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Liothyronine.
AcebutololThe therapeutic efficacy of Liothyronine can be decreased when used in combination with Acebutolol.
Food Interactions
  • Take with or without food.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Liothyronine sodiumGCA9VV7D2N55-06-1SBXXSUDPJJJJLC-UHFFFAOYSA-M
Product Images
International/Other Brands
Tertroxin (Aspen Pharmacare)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CytomelTablet5 ug/1OralPfizer Laboratories Div Pfizer Inc1956-05-08Not applicableUS flag
CytomelTablet5 ug/1OralA S Medication Solutions1956-05-08Not applicableUS flag
CytomelTablet5 mcgOralPfizer Canada Ulc1993-12-31Not applicableCanada flag
CytomelTablet50 ug/1OralPfizer Laboratories Div Pfizer Inc1956-05-08Not applicableUS flag
CytomelTablet25 ug/1OralPhysicians Total Care, Inc.2002-12-30Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Liothyronine SodiumTablet5 ug/1OralGolden State Medical Supply2014-08-282017-02-28US flag
Liothyronine SodiumTablet5 ug/1OralGolden State Medical Supply, Inc.2009-03-20Not applicableUS flag
Liothyronine SodiumTablet25 ug/1OralNorthwind Pharmaceuticals2014-11-12Not applicableUS flag
Liothyronine sodiumTablet5 ug/1OralA-S Medication Solutions2021-02-01Not applicableUS flag
Liothyronine SodiumTablet25 ug/1OralGreenstone LLC2019-06-24Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BITIRON 50 MCG/12.5 MCG TABLET, 100 ADETLiothyronine (12.5 mcg) + Levothyroxine sodium (50 mcg)TabletOralABDİ İBRAHİM İLAÇ SAN. VE TİC. A.Ş.1975-01-21Not applicableTurkey flag
Novothyral - TablettenLiothyronine sodium (100 mcg) + Levothyroxine sodium (20 mcg)TabletOralMerck Gesellschaft Mb H1973-11-26Not applicableAustria flag
ThyrolarLiothyronine sodium (37.5 ug/1) + Levothyroxine sodium (150 ug/1)TabletOralAllergan, Inc.1969-11-212010-09-24US flag
ThyrolarLiothyronine sodium (6.25 ug/1) + Levothyroxine sodium (25 ug/1)TabletOralAllergan, Inc.1969-11-212010-12-10US flag
ThyrolarLiothyronine sodium (25 ug/1) + Levothyroxine sodium (100 ug/1)TabletOralAllergan, Inc.1969-11-212010-06-25US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Adthyza ThyroidLiothyronine (13.5 ug/1) + Levothyroxine (57 ug/1)TabletOralAzurity Pharmaceuticals, Inc.2023-12-18Not applicableUS flag
Adthyza ThyroidLiothyronine (2.25 ug/1) + Levothyroxine (9.5 ug/1)TabletOralAzurity Pharmaceuticals, Inc.2023-12-18Not applicableUS flag
Adthyza thyroidLiothyronine (9 ug/1) + Levothyroxine (38 ug/1)TabletOralAzurity Pharmaceuticals, Inc.2023-02-20Not applicableUS flag
Adthyza ThyroidLiothyronine (9 ug/1) + Levothyroxine (38 ug/1)TabletOralAzurity Pharmaceuticals, Inc.2023-12-18Not applicableUS flag
Adthyza thyroidLiothyronine (18 ug/1) + Levothyroxine (76 ug/1)TabletOralAzurity Pharmaceuticals, Inc.2023-02-20Not applicableUS flag

Categories

ATC Codes
H03AA03 — Combinations of levothyroxine and liothyronineH03AA02 — Liothyronine sodium
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Phenylalanine and derivatives
Alternative Parents
Diphenylethers / Phenylpropanoic acids / Diarylethers / Amphetamines and derivatives / L-alpha-amino acids / Phenoxy compounds / Phenol ethers / O-iodophenols / 1-hydroxy-2-unsubstituted benzenoids / Aralkylamines
show 11 more
Substituents
1-hydroxy-2-unsubstituted benzenoid / 2-halophenol / 2-iodophenol / 3-phenylpropanoic-acid / Alpha-amino acid / Amine / Amino acid / Amphetamine or derivatives / Aralkylamine / Aromatic homomonocyclic compound
show 28 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
iodothyronine, iodophenol, 2-halophenol (CHEBI:18258) / thyroxine, Other amino acids (C02465)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
06LU7C9H1V
CAS number
6893-02-3
InChI Key
AUYYCJSJGJYCDS-LBPRGKRZSA-N
InChI
InChI=1S/C15H12I3NO4/c16-9-6-8(1-2-13(9)20)23-14-10(17)3-7(4-11(14)18)5-12(19)15(21)22/h1-4,6,12,20H,5,19H2,(H,21,22)/t12-/m0/s1
IUPAC Name
(2S)-2-amino-3-[4-(4-hydroxy-3-iodophenoxy)-3,5-diiodophenyl]propanoic acid
SMILES
N[C@@H](CC1=CC(I)=C(OC2=CC(I)=C(O)C=C2)C(I)=C1)C(O)=O

References

Synthesis Reference
US20060246133
General References
  1. Jonklaas J, Burman KD, Wang H, Latham KR: Single-dose T3 administration: kinetics and effects on biochemical and physiological parameters. Ther Drug Monit. 2015 Feb;37(1):110-8. doi: 10.1097/FTD.0000000000000113. [Article]
  2. Sullivan K. (2009). Nurse's drug handbook (8th ed.). Jones and Bartlett Publishers, LLC. [ISBN:978-0-7637-6547-7]
  3. Upfal J. (2007). The Australian Drug Guide (7th ed.). National Library of Australia.
  4. Harrold M. and Zavod R. (2013). Basic Concepts in Medicinal Chemistry. American Society of Health-System Pharmacists. [ISBN:978-1-58528-266-1]
  5. Scott-Moncrieff C. (2015). Canine and feline endocrinology (4th ed.). Elsevier.
  6. Kumar P. (2017). Pharmacology and therapeutics for dentistry (7th ed.). Mosby.
  7. Ashley C. and Dunleavy A. (2014). The renal drug handbook. Caroline Ashley and Aileen Dunleavy.
  8. FDA approvals [Link]
  9. FDA reports [Link]
  10. FDA Approved Drug Products: Cytomel (liothyronine sodium) oral tablets [Link]
  11. FDA Approved Drug Products: Triostat (liothyronine sodium) for intravenous injection [Link]
Human Metabolome Database
HMDB0000265
KEGG Compound
C02465
PubChem Compound
5920
PubChem Substance
46506352
ChemSpider
5707
BindingDB
18860
RxNav
10814
ChEBI
533015
ChEMBL
CHEMBL1544
ZINC
ZINC000003830999
Therapeutic Targets Database
DAP000082
PharmGKB
PA164778866
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
T3
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Liothyronine
PDB Entries
1bsx / 1sn5 / 1xzx / 2h77 / 2h79 / 2piv / 2piw / 3uvv / 3vkx / 4bva
show 4 more
FDA label
Download (213 KB)
MSDS
Download (171 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentDepression1
4CompletedTreatmentDepression / Quality of Life (QOL)1
4CompletedTreatmentHyperlipidemias / Hypopituitarism / Secondary Hypothyroidism1
4CompletedTreatmentMajor Depressive Disorder (MDD)1
4TerminatedTreatmentMajor Depressive Disorder (MDD)1

Pharmacoeconomics

Manufacturers
  • X gen pharmaceuticals inc
  • Jhp pharmaceuticals llc
  • King pharmaceuticals inc
  • Coastal pharmaceuticals inc
  • Mylan pharmaceuticals inc
  • Watson laboratories inc
Packagers
  • Amerisource Health Services Corp.
  • A-S Medication Solutions LLC
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Draxis Specialty Pharmaceuticals Inc.
  • Forest Pharmaceuticals
  • JHP Pharmaceuticals LLC
  • Kaiser Foundation Hospital
  • King Pharmaceuticals Inc.
  • Metrics Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • Paddock Labs
  • Pharmaforce Inc.
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Quality Care
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Schering Corp.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • X-Gen Pharmaceuticals
Dosage Forms
FormRouteStrength
TabletOral25 mcg
TabletOral25 ug/1
TabletOral5 mcg
TabletOral5 ug/1
Injection, solutionIntravenous10 ug/1mL
TabletOral50 ug/1
SolutionOral10 MCG/ML
SolutionOral15 MCG/ML
SolutionOral20 MCG/ML
SolutionOral5 MCG/ML
Solution / dropsOral20 MCG/ML
TabletTopical
TabletOral
TabletOral
InjectionIntravenous10 ug/1mL
Prices
Unit descriptionCostUnit
Triostat 10 mcg/ml vial627.9USD ml
Cytomel 50 mcg tablet1.89USD tablet
Liothyronine Sodium 50 mcg tablet1.69USD tablet
Liothyronine sod 50 mcg tablet1.62USD tablet
Cytomel 25 mcg tablet1.21USD tablet
Cytomel 25 mcg Tablet1.2USD tablet
Cytomel 5 mcg Tablet1.11USD tablet
Liothyronine Sodium 25 mcg tablet1.09USD tablet
Liothyronine sod 25 mcg tablet1.06USD tablet
Cytomel 5 mcg tablet0.89USD tablet
Liothyronine Sodium 5 mcg tablet0.84USD tablet
Liothyronine sod 5 mcg tablet0.81USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)230 ºC'MSDS'
boiling point (°C)563 ºC at 760 mmHg'MSDS'
water solubilityVery slightly soluble'MSDS'
logP3.0'MSDS'
logS-5.22ADME Research, USCD
pKa8.4Harrold M. and Zavod R. 2013. Medicinal Chemistry.
Predicted Properties
PropertyValueSource
Water Solubility0.0195 mg/mLALOGPS
logP0.82ALOGPS
logP2.8Chemaxon
logS-4.5ALOGPS
pKa (Strongest Acidic)0.3Chemaxon
pKa (Strongest Basic)9.48Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count4Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area92.78 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity113.43 m3·mol-1Chemaxon
Polarizability43.92 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.7212
Blood Brain Barrier-0.6886
Caco-2 permeable-0.653
P-glycoprotein substrateNon-substrate0.5321
P-glycoprotein inhibitor INon-inhibitor0.9175
P-glycoprotein inhibitor IINon-inhibitor0.9709
Renal organic cation transporterNon-inhibitor0.8891
CYP450 2C9 substrateNon-substrate0.8309
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6847
CYP450 1A2 substrateNon-inhibitor0.5924
CYP450 2C9 inhibitorNon-inhibitor0.7037
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8459
Ames testNon AMES toxic0.7591
CarcinogenicityNon-carcinogens0.9148
BiodegradationNot ready biodegradable0.9693
Rat acute toxicity2.7082 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9697
hERG inhibition (predictor II)Non-inhibitor0.8508
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-05a9-5090378000-014ef55558b58a3d38f2
MS/MS Spectrum - Quattro_QQQ 10V, N/ALC-MS/MSsplash10-000i-0009001000-1d47041336da63b556e4
MS/MS Spectrum - Quattro_QQQ 25V, N/ALC-MS/MSsplash10-000i-1009001000-15f70073b9018f013c9c
MS/MS Spectrum - Quattro_QQQ 40V, N/ALC-MS/MSsplash10-000i-0009000000-71c231d7a3ab505815ff
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, NegativeLC-MS/MSsplash10-0udi-0000009000-f932659d1e6d8a622985
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, NegativeLC-MS/MSsplash10-0udi-0000009000-6506a7a71dab928abfb0
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, NegativeLC-MS/MSsplash10-0fc0-0700119000-1df6db0e3031eb2739fa
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, NegativeLC-MS/MSsplash10-004i-0900000000-973fc871534b19242cc8
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, NegativeLC-MS/MSsplash10-004i-0900000000-ac3c4a198bb017dc7ccc
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, PositiveLC-MS/MSsplash10-0udi-0000009000-2770ece749a9fa1042f4
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, PositiveLC-MS/MSsplash10-0udi-0000009000-881174c66da97022d645
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, PositiveLC-MS/MSsplash10-0a4i-0000019000-6f798ae76702a3053339
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, PositiveLC-MS/MSsplash10-0a4i-0000219000-d2ca9f0cc3c1b47176b5
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, PositiveLC-MS/MSsplash10-056r-0021915000-6f3810619f383bce651a
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0udi-0000009000-f932659d1e6d8a622985
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0udi-0000009000-6506a7a71dab928abfb0
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-0fc0-0700119000-1df6db0e3031eb2739fa
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-004i-0900000000-973fc871534b19242cc8
LC-MS/MS Spectrum - LC-ESI-QQ , negativeLC-MS/MSsplash10-004i-0900000000-ac3c4a198bb017dc7ccc
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-0000009000-2770ece749a9fa1042f4
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0udi-0000009000-881174c66da97022d645
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-0000019000-6f798ae76702a3053339
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0a4i-0000219000-178f8aeb4d7fe4223eb6
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-056r-0021915000-6f3810619f383bce651a
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0pb9-0000009000-e3d2b054cea9b4f16645
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-052r-0000079000-9ef90d32bab6f2129cff
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-0000009000-059d604bfa90a50fd0ba
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-056r-0005937000-5794c397043c6704260e
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004j-2900058000-a401eb7fdfb5e2bf3004
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0910110000-f04b87b764daa22caf13
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-188.408554
predicted
DarkChem Lite v0.1.0
[M-H]-188.132554
predicted
DarkChem Lite v0.1.0
[M-H]-188.198254
predicted
DarkChem Lite v0.1.0
[M-H]-204.48486
predicted
DeepCCS 1.0 (2019)
[M+H]+188.569554
predicted
DarkChem Lite v0.1.0
[M+H]+188.094654
predicted
DarkChem Lite v0.1.0
[M+H]+187.865254
predicted
DarkChem Lite v0.1.0
[M+H]+207.03267
predicted
DeepCCS 1.0 (2019)
[M+Na]+187.218654
predicted
DarkChem Lite v0.1.0
[M+Na]+187.377654
predicted
DarkChem Lite v0.1.0
[M+Na]+186.975254
predicted
DarkChem Lite v0.1.0
[M+Na]+214.13475
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Isoform Alpha-1: Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.Isoform Al...
Gene Name
THRA
Uniprot ID
P10827
Uniprot Name
Thyroid hormone receptor alpha
Molecular Weight
54815.055 Da
References
  1. Jiang W, Miyamoto T, Kakizawa T, Sakuma T, Nishio S, Takeda T, Suzuki S, Hashizume K: Expression of thyroid hormone receptor alpha in 3T3-L1 adipocytes; triiodothyronine increases the expression of lipogenic enzyme and triglyceride accumulation. J Endocrinol. 2004 Aug;182(2):295-302. [Article]
  2. Kariv R, Enden A, Zvibel I, Rosner G, Brill S, Shafritz DA, Halpern Z, Oren R: Triiodothyronine and interleukin-6 (IL-6) induce expression of HGF in an immortalized rat hepatic stellate cell line. Liver Int. 2003 Jun;23(3):187-93. [Article]
  3. Mai W, Janier MF, Allioli N, Quignodon L, Chuzel T, Flamant F, Samarut J: Thyroid hormone receptor alpha is a molecular switch of cardiac function between fetal and postnatal life. Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10332-7. Epub 2004 Jul 6. [Article]
  4. Sciaudone MP, Yao L, Schaller M, Zinn SA, Freake HC: Diethylenetriaminepentaacetic acid enhances thyroid hormone action by a transcriptional mechanism. Biol Trace Elem Res. 2004 Summer;99(1-3):219-31. [Article]
  5. Timmer DC, Bakker O, Wiersinga WM: Triiodothyronine affects the alternative splicing of thyroid hormone receptor alpha mRNA. J Endocrinol. 2003 Nov;179(2):217-25. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.
Gene Name
THRB
Uniprot ID
P10828
Uniprot Name
Thyroid hormone receptor beta
Molecular Weight
52787.16 Da
References
  1. Bernal J: Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):249-59. [Article]
  2. Gonzalez-Sancho JM, Garcia V, Bonilla F, Munoz A: Thyroid hormone receptors/THR genes in human cancer. Cancer Lett. 2003 Mar 31;192(2):121-32. [Article]
  3. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  4. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  5. Yen PM, Feng X, Flamant F, Chen Y, Walker RL, Weiss RE, Chassande O, Samarut J, Refetoff S, Meltzer PS: Effects of ligand and thyroid hormone receptor isoforms on hepatic gene expression profiles of thyroid hormone receptor knockout mice. EMBO Rep. 2003 Jun;4(6):581-7. [Article]
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
  7. Wu SY, Sadow PM, Refetoff S, Weiss RE: Tissue responses to thyroid hormone in a kindred with resistance to thyroid hormone harboring a commonly occurring mutation in the thyroid hormone receptor beta gene (P453T). J Lab Clin Med. 2005 Aug;146(2):85-94. [Article]
  8. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways (PubMed:24939902). Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.
Specific Function
Chromatin binding
Gene Name
PCNA
Uniprot ID
P12004
Uniprot Name
Proliferating cell nuclear antigen
Molecular Weight
28768.48 Da
References
  1. Punchihewa C, Inoue A, Hishiki A, Fujikawa Y, Connelly M, Evison B, Shao Y, Heath R, Kuraoka I, Rodrigues P, Hashimoto H, Kawanishi M, Sato M, Yagi T, Fujii N: Identification of small molecule proliferating cell nuclear antigen (PCNA) inhibitor that disrupts interactions with PIP-box proteins and inhibits DNA replication. J Biol Chem. 2012 Apr 20;287(17):14289-300. doi: 10.1074/jbc.M112.353201. Epub 2012 Mar 1. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. CYTOMEL (liothyronine) FDA label [File]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Identical protein binding
Specific Function
Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
Gene Name
TTR
Uniprot ID
P02766
Uniprot Name
Transthyretin
Molecular Weight
15886.88 Da
References
  1. Eneqvist T, Lundberg E, Karlsson A, Huang S, Santos CR, Power DM, Sauer-Eriksson AE: High resolution crystal structures of piscine transthyretin reveal different binding modes for triiodothyronine and thyroxine. J Biol Chem. 2004 Jun 18;279(25):26411-6. Epub 2004 Apr 13. [Article]
  2. Palha JA: Transthyretin as a thyroid hormone carrier: function revisited. Clin Chem Lab Med. 2002 Dec;40(12):1292-300. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Major thyroid hormone transport protein in serum.
Gene Name
SERPINA7
Uniprot ID
P05543
Uniprot Name
Thyroxine-binding globulin
Molecular Weight
46324.12 Da
References
  1. Palha JA: Transthyretin as a thyroid hormone carrier: function revisited. Clin Chem Lab Med. 2002 Dec;40(12):1292-300. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Palha JA: Transthyretin as a thyroid hormone carrier: function revisited. Clin Chem Lab Med. 2002 Dec;40(12):1292-300. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Fujiwara K, Adachi H, Nishio T, Unno M, Tokui T, Okabe M, Onogawa T, Suzuki T, Asano N, Tanemoto M, Seki M, Shiiba K, Suzuki M, Kondo Y, Nunoki K, Shimosegawa T, Iinuma K, Ito S, Matsuno S, Abe T: Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12. [Article]
  2. Friesema EC, Docter R, Moerings EP, Stieger B, Hagenbuch B, Meier PJ, Krenning EP, Hennemann G, Visser TJ: Identification of thyroid hormone transporters. Biochem Biophys Res Commun. 1999 Jan 19;254(2):497-501. [Article]
  3. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Abe T, Kakyo M, Tokui T, Nakagomi R, Nishio T, Nakai D, Nomura H, Unno M, Suzuki M, Naitoh T, Matsuno S, Yawo H: Identification of a novel gene family encoding human liver-specific organic anion transporter LST-1. J Biol Chem. 1999 Jun 11;274(24):17159-63. [Article]
  2. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Kullak-Ublick GA, Ismair MG, Stieger B, Landmann L, Huber R, Pizzagalli F, Fattinger K, Meier PJ, Hagenbuch B: Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33. [Article]
  2. Abe T, Unno M, Onogawa T, Tokui T, Kondo TN, Nakagomi R, Adachi H, Fujiwara K, Okabe M, Suzuki T, Nunoki K, Sato E, Kakyo M, Nishio T, Sugita J, Asano N, Tanemoto M, Seki M, Date F, Ono K, Kondo Y, Shiiba K, Suzuki M, Ohtani H, Shimosegawa T, Iinuma K, Nagura H, Ito S, Matsuno S: LST-2, a human liver-specific organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology. 2001 Jun;120(7):1689-99. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Organic anion transporter, capable of transporting pharmacological substances such as digoxin, ouabain, thyroxine, methotrexate and cAMP. May participate in the regulation of membrane transport of ...
Gene Name
SLCO4C1
Uniprot ID
Q6ZQN7
Uniprot Name
Solute carrier organic anion transporter family member 4C1
Molecular Weight
78947.525 Da
References
  1. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T: Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74. Epub 2004 Mar 1. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Virus receptor activity
Specific Function
The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presenc...
Gene Name
SLC10A1
Uniprot ID
Q14973
Uniprot Name
Sodium/bile acid cotransporter
Molecular Weight
38118.64 Da
References
  1. Friesema EC, Docter R, Moerings EP, Stieger B, Hagenbuch B, Meier PJ, Krenning EP, Hennemann G, Visser TJ: Identification of thyroid hormone transporters. Biochem Biophys Res Commun. 1999 Jan 19;254(2):497-501. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Thyroid hormone transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones thyroxine (T4) and rT3. Other potential substrates, such as triiodothyronine (T3), 17-beta-gluc...
Gene Name
SLCO1C1
Uniprot ID
Q9NYB5
Uniprot Name
Solute carrier organic anion transporter family member 1C1
Molecular Weight
78695.625 Da
References
  1. Tohyama K, Kusuhara H, Sugiyama Y: Involvement of multispecific organic anion transporter, Oatp14 (Slc21a14), in the transport of thyroxine across the blood-brain barrier. Endocrinology. 2004 Sep;145(9):4384-91. Epub 2004 May 27. [Article]
  2. Pizzagalli F, Hagenbuch B, Stieger B, Klenk U, Folkers G, Meier PJ: Identification of a novel human organic anion transporting polypeptide as a high affinity thyroxine transporter. Mol Endocrinol. 2002 Oct;16(10):2283-96. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Thyroid hormone transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as the thyroid hormones T3 (triiodo-L-thyronine), T4 (thyroxine) and rT3, and of estrone-3-sulfate and taurocholate.
Gene Name
SLCO4A1
Uniprot ID
Q96BD0
Uniprot Name
Solute carrier organic anion transporter family member 4A1
Molecular Weight
77192.505 Da
References
  1. Fujiwara K, Adachi H, Nishio T, Unno M, Tokui T, Okabe M, Onogawa T, Suzuki T, Asano N, Tanemoto M, Seki M, Shiiba K, Suzuki M, Kondo Y, Nunoki K, Shimosegawa T, Iinuma K, Ito S, Matsuno S, Abe T: Identification of thyroid hormone transporters in humans: different molecules are involved in a tissue-specific manner. Endocrinology. 2001 May;142(5):2005-12. [Article]
  2. Mikkaichi T, Suzuki T, Onogawa T, Tanemoto M, Mizutamari H, Okada M, Chaki T, Masuda S, Tokui T, Eto N, Abe M, Satoh F, Unno M, Hishinuma T, Inui K, Ito S, Goto J, Abe T: Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3569-74. Epub 2004 Mar 1. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Ohtsuki S, Kikkawa T, Mori S, Hori S, Takanaga H, Otagiri M, Terasaki T: Mouse reduced in osteosclerosis transporter functions as an organic anion transporter 3 and is localized at abluminal membrane of blood-brain barrier. J Pharmacol Exp Ther. 2004 Jun;309(3):1273-81. Epub 2004 Feb 4. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Sodium-independent transporter that mediates the update of aromatic acid. Can function as a net efflux pathway for aromatic amino acids in the basosolateral epithelial cells (By similarity).
Gene Name
SLC16A10
Uniprot ID
Q8TF71
Uniprot Name
Monocarboxylate transporter 10
Molecular Weight
55492.07 Da
References
  1. Kim DK, Kanai Y, Chairoungdua A, Matsuo H, Cha SH, Endou H: Expression cloning of a Na+-independent aromatic amino acid transporter with structural similarity to H+/monocarboxylate transporters. J Biol Chem. 2001 May 18;276(20):17221-8. Epub 2001 Feb 20. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Ashida K, Katsura T, Motohashi H, Saito H, Inui K: Thyroid hormone regulates the activity and expression of the peptide transporter PEPT1 in Caco-2 cells. Am J Physiol Gastrointest Liver Physiol. 2002 Apr;282(4):G617-23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Peptide antigen binding
Specific Function
Sodium-independent, high-affinity transport of large neutral amino acids such as phenylalanine, tyrosine, leucine, arginine and tryptophan, when associated with SLC3A2/4F2hc. Involved in cellular a...
Gene Name
SLC7A5
Uniprot ID
Q01650
Uniprot Name
Large neutral amino acids transporter small subunit 1
Molecular Weight
55009.62 Da
References
  1. Uchino H, Kanai Y, Kim DK, Wempe MF, Chairoungdua A, Morimoto E, Anders MW, Endou H: Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition. Mol Pharmacol. 2002 Apr;61(4):729-37. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 19:40